HIV infection follows an extremely variable course, with some individuals staying healthy for more than 15 years while others may become ill and die in fewer than five years. Overall, about one of every five HIV positive people is healthy with no symptoms of HIV after 10 years of infection. A small percentage of HIV positive people have identifiable genetic or virus-related factors identified that may explain the slow (or fast) progression of HIV disease; however, these disease-modifying factors are not common and thus do not explain most of the variability in HIV disease. GB Virus type C (GBV-C) is a human virus that was discovered in 1995. It rapidly became clear that the virus is very common in healthy people. Although GBVC persists in about one in every two to three people infected, extensive studies failed to demonstrate an association with any illness. GBV-C grows in CD4+ T lymphocytes, the same cell that HIV grows in. A number of studies found that HIV-positive people have a very high rate of active (39%) or prior (46%) infection with GBV-C, and furthermore, that HIV-positive people who are co-infected with GBV-C appear to live longer than HIV-positive patients without GBV-C infection. Recently, the Multicenter AIDS Cohort Study group (MACS) tested the best-characterized group of HIV-positive patients in the world, and confirmed that GBV-C infection was associated with prolonged survival, confirmed. In addition, the MACS study found that about 20% of the GBV-C and HIV co-infected individuals lost evidence of GBV-C infection during follow up. Individuals who "lost" the GB virus were almost 6 times more likely to die than those who continued to have active GBV-C infection. We propose to study three large, multicenter cohorts to try to determine why some people lose GBV-C infection. In addition, we will study the association between GBV-C and improved survival in different gender, racial, and ethnic groups. Finally, we will perform exploratory studies designed to identify how GBV-C may improve survival in HIV-positive people. We suspect that it is due to an anti-HIV effect and/or an effect on the host immune system that offers some protection against HIV disease. Determining if this virus is related to delayed HIV disease progression in different groups of people, and understanding how the GB virus slows HIV disease may lead to new approaches to the management of HIV infection.